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Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia.

Thews O, Wolloscheck T, Dillenburg W, Kraus S, Kelleher DK, Konerding MA, Vaupel P - Br. J. Cancer (2004)

Bottom Line: Acute hypoxia reduced the median oxygen partial pressure (pO(2)) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO(2) was significantly improved (median pO(2)=4 mmHg), however not reaching the control level.These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure).In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, 55099 Mainz, Germany. OLTHEWS@uni-mainz.de

ABSTRACT
This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O(2)) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced the median oxygen partial pressure (pO(2)) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO(2) was significantly improved (median pO(2)=4 mmHg), however not reaching the control level. These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure). In animals under chronic inspiratory hypoxia, the number of perfused vessels increased (compared to acute hypoxia), although the perfusion pattern found in control tumours was not reached. In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed. These results suggest that long-term adaptation of tumours to chronic hypoxia in vivo, while not affecting vascularity, does influence the functional status of the microvessels in favour of a more homogeneous perfusion.

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Vascular endothelial growth factor concentration in tumours during chronic inspiratory hypoxia (chronic hypoxia, n=4), acute reduction of the inspiratory O2 fraction for 18 h prior to VEGF measurements (acute hypoxia, n=4) and under normoxic control conditions (n=8).
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fig6: Vascular endothelial growth factor concentration in tumours during chronic inspiratory hypoxia (chronic hypoxia, n=4), acute reduction of the inspiratory O2 fraction for 18 h prior to VEGF measurements (acute hypoxia, n=4) and under normoxic control conditions (n=8).

Mentions: Tumour areas both in the centre and periphery were analysed. n=number of tumours investigated.


Microenvironmental adaptation of experimental tumours to chronic vs acute hypoxia.

Thews O, Wolloscheck T, Dillenburg W, Kraus S, Kelleher DK, Konerding MA, Vaupel P - Br. J. Cancer (2004)

Vascular endothelial growth factor concentration in tumours during chronic inspiratory hypoxia (chronic hypoxia, n=4), acute reduction of the inspiratory O2 fraction for 18 h prior to VEGF measurements (acute hypoxia, n=4) and under normoxic control conditions (n=8).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747687&req=5

fig6: Vascular endothelial growth factor concentration in tumours during chronic inspiratory hypoxia (chronic hypoxia, n=4), acute reduction of the inspiratory O2 fraction for 18 h prior to VEGF measurements (acute hypoxia, n=4) and under normoxic control conditions (n=8).
Mentions: Tumour areas both in the centre and periphery were analysed. n=number of tumours investigated.

Bottom Line: Acute hypoxia reduced the median oxygen partial pressure (pO(2)) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO(2) was significantly improved (median pO(2)=4 mmHg), however not reaching the control level.These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure).In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed.

View Article: PubMed Central - PubMed

Affiliation: Institute of Physiology and Pathophysiology, University of Mainz, Duesbergweg 6, 55099 Mainz, Germany. OLTHEWS@uni-mainz.de

ABSTRACT
This study investigated long-term microenvironmental responses (oxygenation, perfusion, metabolic status, proliferation, vascular endothelial growth factor (VEGF) expression and vascularisation) to chronic hypoxia in experimental tumours. Experiments were performed using s.c.-implanted DS-sarcomas in rats. In order to induce more pronounced tumour hypoxia, one group of animals was housed in a hypoxic atmosphere (8% O(2)) for the whole period of tumour growth (chronic hypoxia). A second group was acutely exposed to inspiratory hypoxia for only 20 min prior to the measurements (acute hypoxia), whereas animals housed under normal atmospheric conditions served as controls. Acute hypoxia reduced the median oxygen partial pressure (pO(2)) dramatically (1 vs 10 mmHg in controls), whereas in chronically hypoxic tumours the pO(2) was significantly improved (median pO(2)=4 mmHg), however not reaching the control level. These findings reflect the changes in tumour perfusion where acutely hypoxic tumours show a dramatic reduction of perfused tumour vessels (maybe the result of a simultaneous reduction in arterial blood pressure). In animals under chronic inspiratory hypoxia, the number of perfused vessels increased (compared to acute hypoxia), although the perfusion pattern found in control tumours was not reached. In the chronically hypoxic animals, tumour cell proliferation and tumour growth were significantly reduced, whereas no differences in VEGF expression and vascular density between these groups were observed. These results suggest that long-term adaptation of tumours to chronic hypoxia in vivo, while not affecting vascularity, does influence the functional status of the microvessels in favour of a more homogeneous perfusion.

Show MeSH
Related in: MedlinePlus